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Molecular mechanisms of pathology and treatment in D iamond B lackfan A naemia
Author(s) -
Horos Rastislav,
Lindern Marieke
Publication year - 2012
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12058
Subject(s) - diamond–blackfan anemia , ribosome biogenesis , erythropoiesis , haploinsufficiency , ribosomal protein , ribosome , translation (biology) , context (archaeology) , biology , ribosomal rna , protein biosynthesis , mutation , microbiology and biotechnology , messenger rna , gene , genetics , rna , medicine , anemia , phenotype , paleontology
Summary Diamond Blackfan Anaemia ( DBA ) is a rare congenital pure red cell aplasia that may be associated with facio‐skeletal developmental defects. The disease is caused by mutations in one of at least ten ribosomal proteins, which results in haploinsufficiency and an imbalance between the synthesis of rRNA and ribosomal proteins during ribosome biogenesis. Such imbalance results in stabilization and activation of the tumour suppressor gene TP 53 . The loss of ribosomes also results in reduced mRNA translation capacity, and may affect translation of specific erythroid transcripts more than average. The contribution of these two mechanisms to impaired erythropoiesis is discussed. The most effective and relatively safe therapy is treatment with glucocorticoid hormone, but responsiveness differs between patients. The molecular and cellular mechanisms involved in treatment are discussed in the context of DBA .